The role of slow and fast protein motions in allosteric interactions

Shiou Ru Tzeng, Charalampos G. Kalodimos

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Allostery is fundamentally thermodynamic in nature. Long-range communication in proteins may be mediated not only by changes in the mean conformation with enthalpic contribution but also by changes in dynamic fluctuations with entropic contribution. The important role of protein motions in mediating allosteric interactions has been established by NMR spectroscopy. By using CAP as a model system, we have shown how changes in protein structure and internal dynamics can allosterically regulate protein function and activity. The results indicate that changes in conformational entropy can give rise to binding enhancement, binding inhibition, or have no effect in the expected affinity, depending on the magnitude and sign of enthalpy–entropy compensation. Moreover, allosteric interactions can be regulated by the modulation a low-populated conformation states that serve as on-pathway intermediates for ligand binding. Taken together, the interplay between fast internal motions, which are intimately related to conformational entropy, and slow internal motions, which are related to poorly populated conformational states, can regulate protein activity in a way that cannot be predicted on the basis of the protein’s ground-state structure.

Original languageEnglish (US)
Pages (from-to)251-255
Number of pages5
JournalBiophysical Reviews
Volume7
Issue number2
DOIs
StatePublished - Jun 16 2015

Keywords

  • Catabolite activator protein
  • Cyclic nucleotide-binding
  • NMR spectroscopy

Fingerprint Dive into the research topics of 'The role of slow and fast protein motions in allosteric interactions'. Together they form a unique fingerprint.

Cite this